# A protein adaptor mediating Ap4A-dependent control of protein acetylation

## TL;DR

This study reveals how a protein called AcuB, regulated by a stress molecule, inhibits a deacetylase in bacteria, linking stress response to protein acetylation.

## Contribution

The study identifies AcuB as a novel Ap4A-regulated inhibitor of the deacetylase AcuC in bacteria.

## Key findings

- AcuB forms a stable complex with AcuC to inhibit its activity.
- Ap4A enhances AcuB's inhibitory effect by binding to its CBS domain.
- Ap4A connects stress signaling to acetylation control and acetyl-CoA biosynthesis.

## Abstract

Reversible lysine acetylation is a highly conserved post-translational modification across all domains of life controlling diverse cellular processes such as metabolism and gene expression. However, the regulation of protein acetylation remains poorly understood. Here, we report a regulatory system in Bacillus subtilis that controls the activity of the histone deacetylase (HDAC)-like protein AcuC, which has multiple substrates including acetyl-CoA synthetase and translation elongation factor. We show that AcuC is inhibited via formation of a stable complex with the hitherto uncharacterized protein AcuB. We furthermore demonstrate that the alarmone diadenosine tetraphosphate (Ap4A) binds to the cystathionine beta-synthase (CBS) domain of AcuB, thereby stabilizing AcuB and further enhancing the inhibition of AcuC. In summary, this study identifies AcuB as an Ap4A regulated deacetylation inhibitor, revealing a uncharacterized molecular mechanism to control HDAC-like proteins. Thus, the alarmone Ap4A modulates protein (de)acetylation, pointing towards a regulatory network that connects stress response, protein acetylation, and acetyl-CoA biosynthesis.

This study identifies AcuB as a conserved inhibitor of the deacetylase AcuC in bacteria. AcuB directly suppresses AcuC activity, and this inhibition is enhanced the alarmone diadenosine tetraphosphate, linking stress signaling to acetylation control.